Safety and Immunogenicity of Prime-Boost Vesicular Stomatitis Virus (VSV) Ebola Vaccine in Healthy Adults (V920-002)

NCT02280408 | Completed Phase 1 Results

• 2 other identifiers: V920-002NLG0207 (Study 15-I-0001)
• Study Type: interventional
• Target: 39
• Locations: 0 countries
• Sites: N/A

Brief Summary

Ebola virus has infected and killed people, mostly in Africa. In 2014, the Zaire ebolavirus (ZEBOV) has affected several thousand people. There is no approved effective way to treat or prevent Ebola. Researchers are trying to develop a vaccine for it. This is a study of the anti-Ebola vaccine vesicular stomatitis virus (VSV) ZEBOV (V920; BPSC-1001) to see if it is safe and to see how it affects people's immune system.

Conditions

Ebola Viruses

Outcome Measures

Primary Outcomes (8)

• Percentage of Participants With 1 or More Unsolicited AE : Vaccination 1

  An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study drug or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. An unsolicited AE was an AE other than those specifically designated local or systemic. The percentage of participants that experienced at least 1 unsolicited AE was summarized.

  Up to 28 days post vaccination 1 (From Day 1 up to Day 28)

• Percentage of Participants With 1 or More Unsolicited AE : Vaccination 2

  An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study drug or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. An unsolicited AE was an AE other than those specifically designated local or systemic. The percentage of participants that experienced at least 1 unsolicited AE was summarized.

  Up to 28 days post vaccination 2 (From Day 29 to Day 56)

• Percentage of Participants With 1 or More Solicited Systemic Adverse Event (AE) by Severity: Vaccination 1

  A solicited AE was a predetermined specific event. The solicited systemic AEs for this study were the following: redness, swelling, or pain at site of injection, subjective and objective fever, chills, sweats, myalgia, arthralgia, fatigue, headache and gastrointestinal symptoms (nausea, vomiting, abdominal pain, and/or diarrhea). All AEs were assessed for severity by the investigator according to the Food and Drug Administration(FDA's) Guidance "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials" and were classified into 4 categories: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3) and Potentially Life-Threatening (Grade 4). The percentage of participants that experienced at least 1 solicited systemic AE were summarized by grade.

  Up to 14 days post vaccination 1 (From Day 1 up to Day 14)

• Percentage of Participants With 1 or More Solicited Systemic AE by Severity: Vaccination 2

  A solicited AE was a predetermined specific event. The solicited systemic AEs for this study were the following: redness, swelling, or pain at site of injection, subjective and objective fever, chills, sweats, myalgia, arthralgia, fatigue, headache and gastrointestinal symptoms (nausea, vomiting, abdominal pain, and/or diarrhea). All AEs were assessed for severity by the investigator according to the Food and Drug Administration(FDA's) Guidance "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials" and were classified into 4 categories: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3) and Potentially Life-Threatening (Grade 4). The percentage of participants that experienced at least 1 solicited systemic AE were summarized by grade.

  Up to 14 days post vaccination 2 (Day 29 up to Day 42)

• Percentage of Participants With One or More Serious Adverse Event

  An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the study vaccine. An SAE is an AE that results in death, is life-threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, or is another important medical event. The percentage of participants that experienced 1 or more SAEs was summarized.

  Up to Day 56 (Day 1 up to Day 56)

• Percentage of Participants With 1 or More Solicited Local Injection-site AE by Severity: Vaccination 1

  A solicited AE was a predetermined specific event. The solicited local AEs for this study were the following: Local reactogenicity signs and symptoms include pain, erythema (redness), and induration (swelling). All AEs were assessed for severity by the investigator according to the Food and Drug Administration(FDA's) Guidance "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials" and were classified into 4 categories: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3) and Potentially Life-Threatening (Grade 4). The percentage of participants that experienced at least 1 solicited local AE was summarized by grade.

  Up to 14 days post vaccination 1 (Day 1 to Day 14)

• Percentage of Participants With 1 or More Solicited Local Injection-site AE by Severity: Vaccination 2

  A solicited AE was a predetermined specific event. The solicited local AEs for this study were the following: Local reactogenicity signs and symptoms include pain, erythema (redness), and induration (swelling). All AEs were assessed for severity by the investigator according to the Food and Drug Administration(FDA's) Guidance "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials" and were classified into 4 categories: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3) and Potentially Life-Threatening (Grade 4). The percentage of participants that experienced at least 1 solicited local AE was summarized by grade.

  Up to 14 days post vaccination 2 (Day 29 up to Day 42)

• Percentage of Participants With Early Discontinuation of Vaccination

  The percentage of participants that had vaccination discontinued for any reason was summarized.

  Up to Day 28

Secondary Outcomes (8)

• Geometric Mean Titers of Zaire Ebolavirus-(ZEBOV)-Specific Immunoglobin G (IgG) Antibodies: Day 28

  Day 28

• Geometric Mean Titers of ZEBOV-specific IgG Antibodies: Day 56

  Day 56 (28 days post vaccination 2)

• Geometric Mean Titers of ZEBOV-specific Neutralizing Antibodies: Day 28

  Day 28 (28 days post vaccination 1)

• Geometric Mean Titers of ZEBOV-specific Neutralizing Antibodies: Day 56

  Day 56 (28 days post vaccination 2)

• Percentage of Participants Who Seroconvert: Day 28

  Day 28 (28 days post vaccination 1)

Study Arms (4)

3x10^6 plaque-forming units (pfu) Vaccine Cohort

EXPERIMENTAL

Participants will receive a 1-mL intramuscular injection of V920 3x10\^6 pfu in the deltoid on Day 0 and Day 28.

Biological: V920

2x10^7 pfu Vaccine Cohort

EXPERIMENTAL

Participants will receive a 1-mL intramuscular injection of V920 2x10\^7 pfu in the deltoid on Day 0 and Day 28.

Biological: V920

1x10^8 pfu Vaccine Cohort

EXPERIMENTAL

Participants will receive a 1-mL intramuscular injection of V920 1x10\^8 pfu in the deltoid on Day 0 and Day 28.

Biological: V920

Placebo Cohort

PLACEBO COMPARATOR

Participants will receive a 1-mL intramuscular injection of placebo in the deltoid on Day 0 and Day 28.

Other: Placebo

Interventions

Placebo OTHER

Normal saline placebo.

Placebo Cohort

V920 BIOLOGICAL

Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10\^6, 2x10\^7, or 1x10\^8 pfu.

1x10^8 pfu Vaccine Cohort; 2x10^7 pfu Vaccine Cohort; 3x10^6 plaque-forming units (pfu) Vaccine Cohort

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy male or females, ages 18 to 65 (inclusive) at the time of screening
• Females of childbearing potential and all males, must be willing to use effective methods of contraception, from at least 14 days prior to vaccination through Day 56 which would include:
• Oral contraceptives, either combined or progestogen alone
• injectable progestogen
• implants of etonogestrel or levonorgestrel
• oestrogenic vaginal ring
• percutaneous contraceptive patches
• intrauterine device or intrauterine system
• male partner sterilization
• male condom combined with a spermicide
• Must be willing to minimize blood and body fluid exposure of others for at least 7 days after vaccination, which includes:
• Use of effective barrier prophylaxis, such as latex condoms, during any sexual interaction (regardless of childbearing status or sexual orientation)
• Avoiding the sharing of needles, razors, eating utensils, drinking from the same cup, or toothbrushes
• Avoiding open-mouth kissing
• Must be willing to forgo blood donation for one year

You may not qualify if:

• FACTORS THAT INCREASE RISK TO THE SUBJECT:
• Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to:
• A process that would affect the immune response
• A process that would require medication that affects the immune response
• Any contraindication to repeated injections or blood draws
• A condition that requires active medical intervention or monitoring to avert grave danger to the participant's health or well-being during the study period
• A condition or process for which signs or symptoms could be confused with reactions to vaccine
• Active malignancy
• Asplenia
• History of Guillain-Barré Syndrome
• History of neurological or neuropsychiatric disorder that may either increase risk (history of encephalitis, narcolepsy, stroke, depression, bipolar disorder, seizure, etc.) or could interfere with the assessment of safety (e.g., frequent headaches)
• History of autoimmune disease
• History of hemoglobinopathy or a coagulopathy
• Women who are breast-feeding
• Positive urine or serum pregnancy test

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• BioProtection Systems Corporation: collaborator

Related Publications (2)

• Coller BG, Blue J, Das R, Dubey S, Finelli L, Gupta S, Helmond F, Grant-Klein RJ, Liu K, Simon J, Troth S, VanRheenen S, Waterbury J, Wivel A, Wolf J, Heppner DG, Kemp T, Nichols R, Monath TP. Clinical development of a recombinant Ebola vaccine in the midst of an unprecedented epidemic. Vaccine. 2017 Aug 16;35(35 Pt A):4465-4469. doi: 10.1016/j.vaccine.2017.05.097. Epub 2017 Jun 21.

  PMID: 28647166 DERIVED

• Regules JA, Beigel JH, Paolino KM, Voell J, Castellano AR, Hu Z, Munoz P, Moon JE, Ruck RC, Bennett JW, Twomey PS, Gutierrez RL, Remich SA, Hack HR, Wisniewski ML, Josleyn MD, Kwilas SA, Van Deusen N, Mbaya OT, Zhou Y, Stanley DA, Jing W, Smith KS, Shi M, Ledgerwood JE, Graham BS, Sullivan NJ, Jagodzinski LL, Peel SA, Alimonti JB, Hooper JW, Silvera PM, Martin BK, Monath TP, Ramsey WJ, Link CJ, Lane HC, Michael NL, Davey RT Jr, Thomas SJ; rVSVDeltaG-ZEBOV-GP Study Group. A Recombinant Vesicular Stomatitis Virus Ebola Vaccine. N Engl J Med. 2017 Jan 26;376(4):330-341. doi: 10.1056/NEJMoa1414216. Epub 2015 Apr 1.

  PMID: 25830322 DERIVED

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2014
• First Posted: October 31, 2014
• Study Start: October 7, 2014
• Primary Completion: December 10, 2015
• Study Completion: December 10, 2015
• Last Updated: July 12, 2019
• Results First Posted: July 12, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will share